Degradable polymers like polyesters and polycarbonates have been used for years within the medical device industry as sutures and various fixation devices such as plates, pins and screws to hold small bone fragments together during healing. The activity in the field of three-dimensional (3D) scaffolding structures for the purpose of bridging tissue gaps and giving the cells a scaffold to populate and proliferate on has been considerable, especially in the last 15 years. However, the limited number of such devices in today's market indicates the difficulty in providing a scaffold that fits the surgeons' needs in terms of tissue regeneration, ease of use and problem-free healing. One of the very first patent applications describing a porous 3D structure using synthetic degradable polymers was filed in 1974, U.S. Pat. No. 3,902,497, disclosing an absorbable sponge that could be used as a hemostatic and left to degrade and disappear inside the human body. In 1977 another application was filed, U.S. Pat. No. 4,186,448, describing a porous plug for regeneration of bone in bone defects or voids. This can be said to be the beginning of the search of synthetic degradable scaffolds that would support cells during the early phase of proliferation, and which also provided voids in form of interconnected pores to allow for a homogeneous population of the entire scaffold. Today, still the same technique is used and explored by thousands of researchers all over the world in search for the ultimate scaffold. The methods of making porous scaffolds have been greatly refined over the last years and several techniques are available. New emerging techniques such as 3D printing, 3D knitting and electrospinning to mention a few are actively being explored in new scaffolds for various tissue engineering applications with various results (Sears N. A. et al., Tissue Engineering: Part B, Volume 22, Number 4, pages 298-311, 2016; Kim J. J. et al., Acta Biomaterialia, Volume 41, pages 17-26, 2016; Wang X. et al., Journal of the mechanical behavior of biomedical materials, Volume 4, pages 922-932, 2011). In US20140222161A1, U.S. Pat. No. 5,514,181, and US20120010636A1, other types of three-dimensional medical implants are described.
One of the greatest challenges for the perfect scaffold is that it shall combine an adequate modulus required by the surrounding tissue to avoid modulus mismatch and at the same time have an open structure to allow for tissue ingrowth and vascularization to avoid apoptosis in the scaffold interior.
Furthermore, it is difficult to combine different scaffold characteristics or even different materials into one scaffold since porous materials made by solid leaching or phase separation techniques do yield a very similar structure throughout the entire scaffold. With the use of 3D printing we may overcome the difficulty in combining different materials and also different designs into one scaffold. There are however still several obstacles to overcome before it is possible to make scaffolds which possess a certain predefined design, which are easy to apply/adapt at the defect site and which have the required mechanical strength needed for various specific clinical defects.
The lack of pliability is often a tradeoff since the scaffold needs to possess certain rigidity in order for the matrix to withstand the natural load situation over the scaffold after implantation. Especially in soft tissue applications, the scaffold should be resilient enough to follow the load situation and to regain shape with minimal hysteresis when no load is acting upon it until the scaffold has been fully populated by cells overtaking the load supporting function. For hard tissue applications, pliability is not such a concern but the concept of using different materials and designs to achieve different clinical results at various sections of the scaffold is still an unsolved challenge, i.a. soft tissue integration and anchoring of the device in one section and bone tissue regeneration in the other section. Current research within material and/or processing technology have not yet been able to mimic the properties of a fully functional matrix for soft tissue regeneration which, from a doctor's perspective should be easy to apply, should have minimal modulus mismatch and possess pliable and resilient properties without compromising with the mechanical requirements.
Modern hydrogels may seem to be the perfect choice of soft and resilient biomaterial, but they are fragile with poor mechanics and must be made and used at the bedside. Some of them can be freeze dried and rehydrated before use, but this presents the doctor with additional work and distraction from the patient and the ongoing surgery. The lack of possibility to anchor/fasten the hydrogel matrix is another great drawback with these types of scaffolds since most scaffolds will need suturing or some kind of tacks to keep them in place until it is anchored by new tissue deposited within the scaffold.
Current degradable scaffolds or matrices, aimed at short term support during repair or regeneration of new tissue in various clinical defects, have several drawbacks and among them is the lack of pliability of most scaffolds. Lack of pliability often leads to an overall modulus mismatch with surrounding tissue that may trigger an excess of inflammatory reactions that may compromise the early healing process. A prerequisite for a functional scaffold is to provide space for new tissue to populate. If the scaffold is made too soft or pliable there is an ultimate risk for collapse of the porous structure especially if the clinical situation exposes the scaffold to static or dynamic loads. With current processes for making porous scaffolds which can be used for tissue regeneration or augmentation there are also limitations when it comes to fabrication of multilayer, gradient or multiphase scaffolds that could exhibit different physiochemical properties in various sections of the scaffold.